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PF-07302048 (BNT162 RNA-Based COVID-19 Vaccines)
Protocol C4591001

5. If any participant dies or requires ICU admission due to SARS-CoV-2 infection; if this
stopping rule is met, all available clinical and preclinical safety and immunogenicity data
should be reviewed to evaluate for enhanced COVID-19.

8.2.4. Surveillance of Events That Could Represent Enhanced COVID-19 and Phase 2/3
Stopping Rule
Participants in all phases of the study will be surveilled for potential COVID-19 illness from
Visit 1 onwards (see Section 8.13).

As this is a sponsor open-label study during Phase 1, the sponsor will conduct unblinded
reviews of the data during the course of the study, including for the purpose of safety
assessment. All NAAT-confirmed cases in Phase 1 will be reviewed contemporaneously by
the IRC and the DMC (see Section 9.6).

In Phase 2/3, the unblinded team supporting the DMC, including an unblinded medical
monitor, will review cases of severe COVID-19 as they are received and will review AEs at
least weekly for additional potential cases of severe COVID-19. At any point, the unblinded
team may discuss with the DMC chair whether the DMC should review cases for an adverse
imbalance of cases of COVID-19 and/or severe COVID-19 between the vaccine and placebo
groups.

The purpose of these reviews will be to identify whether any features of each case appear
unusual, in particular greater in severity, compared to available information at the time of
review. Indicators of severity may include accelerated deterioration, need for hospitalization,
need for ventilation, or death. Observed rates of these indicators will be compared with what
could be expected in a similar population to the study participants based upon available
information at the time of review.

Stopping and alert rules will be applied as follows. The stopping rule will be triggered when
the 1-sided probability of observing the same or a more extreme case split is 5% or less when
the true incidence of severe disease is the same for vaccine and placebo participants, and alert
criteria are triggered when this probability is less than 11%. In addition, when the total
number of severe cases is low (15 or less), the unblinded team supporting the DMC will
implement the alert rule when a reverse case split of 2:1 or worse is observed. For example,
at 3 cases 2:1, at 4 cases 3:1, etc. Below 15 cases, this rule is more rigorous than requiring
the probability of an observed adverse split or worse be <11%. Further details can be found
in Section 10.7.

8.2.5. Randomization and Vaccination After a Stopping Rule Is Met
Once the IRC (if in Phase 1) and DMC (all phases) have reviewed the safety data and
provided guidance, a notification will be sent from the sponsor to the sites with guidance on
how to proceed.

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